Is AP3B2 p.Ala6fs (c.15del) pathogenic?

AP3B2 p.Ala6fs (c.15del) is classified Pathogenic in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-29). Very rare (popmax 8.91e-05%, nfe).

How common is AP3B2 p.Ala6fs (c.15del) in the general population?

AP3B2 p.Ala6fs (c.15del) is very rare (popmax 8.91e-05%, nfe) (gnomAD).

AP3B2 p.Ala6fs

c.15del · rs1409976651 · VCV1369595

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.91e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.6	GERP 1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.91e-05% European (non-Finnish) · 1/1,122,622 alleles

Overall 7.46e-05% 1/1,340,656 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AP3B2
Protein: p.Ala6fs
Coding: c.15del
MANE Select: NM_001278512
dbSNP: rs1409976651
Type: Deletion
Location: chr15:82709692 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 6: the 'disordered' region

Full AP3B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3B2 p.Ala6Thr Uncertain significance ★ ⚠ same residue
AP3B2 p.Pro993fs Pathogenic/Likely pathogenic ★★ same type
AP3B2 p.Tyr94fs Pathogenic/Likely pathogenic ★★ same type
AP3B2 c.1489-5_1489-3del Benign/Likely benign ★★ same type
AP3B2 c.2262-34_2268del Likely pathogenic ★ same type
AP3B2 p.Asn220fs Pathogenic ★ same type
AP3B2 p.Glu152fs Likely pathogenic ★ same type
AP3B2 p.Glu613fs Pathogenic ★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ap3b2-p-ala6fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown